In the twentieth century, as the average life span of human has been increasing with the rapid development of life science and medicine, new social problems including increased population ratio of older people are coming to the front, especially, the geriatric neuronal diseases such as stroke, Alzheimer's disease (AD), Parkinson's disease (PD) etc., which are fatal functional disorder of neuronal system, have been increased.
The growth, differentiation and death of neuronal cell in neuronal system are important control processes in general development the establishment of tissue specific function and the maintenance of homeostasis respectively.
Cerebrovascular disease is classified into two types, hemorrhagic brain disease and ischemic brain disease: the hemorrhagic brain disease such as cerebral hemorrhage occurs mainly by bleeding of cerebral vessels and the ischemic brain disease frequently occurring in older people is caused by the occlusion of cerebral vessels.
In case that temporary cerebral ischemia occurs, the supply of oxygen and glucose to brain is prevented and several syndrome such as ATP decrease and edema follows, which causes to exclusive range of brain injury as the result. After the considerable time lapses, the apoptosis of neuronal cell occurs, which is called as delayed neuronal death. The effect on the delayed type of neuronal death is performed by transient forebrain ischemic model using Mongolian gerbil and it has been reported that neuronal death occurs at CA1 region in hippocampus four days after the inducement of cerebral ischemia for 5 mins (Kirino T et al, Acta Neuropathol., 62 pp 201-208, 1984; Kirino T, Brain Res., 239, pp 57-69, 1982).
It has been reported that the neuronal death is caused by two mechanism; one is excitotoxic neuronal death mechanism; cerebral ischemia causes to excessive accumulation of outer glutamate and those glutamate are influxed into inner cell which causes to neuronal death by excessive accumulation of intracellular calcium ion (Kang T. C. et al, J. Neurocytol., 30, pp 945-955, 2001) and another is oxidative neuronal death; the ischemia-reperfusion causing abrupt supply of oxygen results in the increase of free radical to give rise to the injury of DNA and cytoplasm (Won M. H. et al, Brain Res., 836, pp 70-78, 1999; Sun A. Y. et al, J. Biomed. Sci., 5, pp 401-141, 1998; Flowers F et al, New Horiz, 6, pp 169-180, 1998).
On the base of those mechanism study, there have been endeavored to develop effectively inhibiting substance of neuronal death or the mechanism thereof till now, however, neuroprotective agents have been nearly not yet found.
t-PA (tissue plasminogen activator), sole approved cerebral ischemia treating agent in FDA and sold in the market is a thrombolytic agent dissolving thrombus causing cerebral ischemia and inducing rapid supply of oxygen and glucose. Accordingly, it could not protect neuronal cell directly therefore it should be used urgently. Furthermore, since it is a thrombolytic agent, hemorrhagic cerebral disease occurs in case that it is administrated in over dose or too frequently.
MK-801, a potent NMDA receptor blocker effectively inhibiting initial calcium ion influx had been on clinical trial however it was abandoned because of its adverse action.
In Korea, lots of health care foods containing natural substance have been on the market however most of those are not yet authorized by scientific test and abused to give rise to scientific problems in the end.
Accordingly, it have been still needed to develop novel natural resource effective in treating and preventing cerebral disease through substantive and scientific experiments till now.
Panax ginseng C. A. Meyer belonged to Araliaceae, is distributed in Asian countries as well as other countries. It has been used as materials of Chinese medicine as a restorative and reported to comprise various ginseng saponins such as ginsenoside. Rb1, Rb2, Rc, Rd, Re, panaxadiol, panaxatriol, kaempferol etc (Chung B. S. and Shin M. K.; HyangyakDaesacheon, Youngrimsa, pp 439-444, 1998).
Acanthopanax senticosus HARMS belonged to Araliaceae, is distributed in humid area of Korea, Siberia etc. It has been used as materials of Chinese medicine as adatogenic activities, anti-inflammatory agents and reported to comprise various glycosides such as saponins, eleutherosides, essential oil etc (Chung B. S. and Shin M. K.; HyangyakDaesacheon, Youngrimsa, pp 433-435, 1998).
Angelica sinensis DIELS belonged to Umbelliferae, is distributed in China. It has been used as materials of Chinese medicine as a treating agent of various gynopathic diseases and reported to comprise various components such as ligustilide, butylidene phthalide, cnilide, isocnilide, nicotinic acid, sitosterol, essential oil etc (Chung B. S. and Shin M. K.; HyangyakDaesacheon, Youngrimsa, pp 406-408, 1998).
Scutellaria baicalensis GEORGI belonged to Labiatae, is distributed in Korea, China, Siberia etc. It has been used as materials of Chinese medicine as a diuretics, anti-inflammatory agent, cholagogue, etc and reported to comprise various components such as baicalin, baicalin, woginin, wogonoside, scutellarein, hispidulin etc (Chung B. S. and Shin M. K.; HyangyakDaesacheon, Youngrimsa, pp 864-865, 1998).
However, there has been not reported or disclosed about therapeutic effect for brain disease of the crude drug complex comprising Panax ginseng C. A. Meyer, Acanthopanax senticosus HARMS, Angelica sinensis DIELS, Scutellaria baicalensis GEORGI, in any of above cited literatures, the disclosures of which are incorporated herein by reference.
To investigate an effect of the extract of above described crude drug complex on the neuronal growth and differentiation through several biochemical experiments and to confirm whether the extract play an important role in inhibiting neuronal apoptosis, main cause of stroke and neurodegenerative diseases, the inventors of the present invention have intensively carried out 4 sensory motor function tests using animal model, and finally completed present invention by confirming that the extract inhibit the neuronal apoptosis, and show neuroprotective activity.
These and other objects of the present invention will become apparent from the detailed disclosure of the present invention provided hereinafter.